1. Field of the Invention
The invention relates to methods and compositions useful for magnetic resonance imaging (MRI) of membrane potential.
2. Description of the Related Art
Magnetic resonance imaging (MRI) contrast agents are known in the art and are used to improve contrast amongst various soft tissues. Conventional magnetic resonance contrast agents interact with water to alter the signal from water protons that provide the image. Such contrast agents, however, are insensitive to membrane potential. Consequently, magnetic resonance imaging, while providing excellent spatial resolution in images of biologic structures, provides little or no information about the electrical activity of the imaged tissues. For electrically-excitable tissues such as neurons, and muscles it would be advantageous to obtain molecular resonance based images of membrane potential from which tissue function could be assessed in a non-invasive manner.
U.S. Pat. No. 5,325,854 to Enholm titled “Magnetic Resonance Imaging” provides ionic or ionizable paramagnetic substances capable of associating with cell membrane lipids to provide a contrast agent that has an electron spin resonance (ESR) signature. The association of the ESR component with the membrane changes the ESR signature. These substances can be used with a modification of molecular resonance imaging known as electron spin resonance enhanced magnetic resonance imaging (ESREMRI) to image biological electromagnetic activity, but cannot be used with conventional MRI equipment.
U.S. Pat. No. 5,532,006 to Lauterbur et al. titled “Magnetic Gels Which Change Volume in Response to Voltage Changes for MRI” relies on electric-field induced volume changes of a matrix in which is distributed a superparamagnetic component. Changes in the specific volume of the matrix affect the response of the distributed component to the magnetic field and so provide a basis for imaging membrane potential. The requirement in that the compositions be a matrix, however, may limit the ability to safely administer the disclosed compositions or to have them partition readily out of the vasculature into other tissue compartments.
Thus there is a need in the art for contrast agents that act as MRI probes of membrane potential that can be used with conventional MRI equipment and that do not rely changes in matrix volume to produce a signal. The present invention provides for these and other advantages over the prior art.